Accepted Article
Received Date : 23-Jul-2014 Revised Date : 10-Nov-2014 Accepted Date : 09-Feb-2015 Article type
: Research Article
Gestational diabetes: a red flag for future Type 2 diabetes in pregnancy? A retrospective analysis
N. W. Cheung1,2, A. Lih1,2, S. M. Lau1, K. Park2, S. Padmanabhan1 and A. McElduff3
1
Department of Diabetes & Endocrinology, Westmead Hospital, Sydney, 2Department of
Diabetes & Endocrinology, Nepean Hospital, Sydney, 3The Northern Sydney Endocrine Centre
and Royal North Shore Hospital, Sydney, Australia
Correspondence to: N. Wah Cheung. E-mail: [email protected]
What’s new? •
We found that almost half the women with Type 2 diabetes in pregnancy previously had gestational diabetes.
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/dme.12723 This article is protected by copyright. All rights reserved.
Accepted Article
•
Gestational diabetes is an opportunity to discuss and improve future pregnancy planning, particularly with respect to Type 2 diabetes in pregnancy.
Abstract Aims This study sought to understand the relationship between Type 2 diabetes in pregnancy and previous gestational diabetes (GDM), and determine whether a previous pregnancy with GDM was associated with subsequent better pregnancy planning. Methods A retrospective review of medical records of women with Type 2 diabetes in pregnancy was conducted at three teaching hospitals to ascertain whether they had earlier GDM, and to determine whether this is associated with differences in measures of pregnancy planning and diabetes management. Results Of 172 index pregnancies affected by Type 2 diabetes, in 76 (44%) cases, the mother had a previous history of GDM. Within this cohort, a diagnosis of ‘overt diabetes in pregnancy’, made on the basis of a GTT result during pregnancy in the WHO diabetic range with persistent diabetes post partum, was more common among women who had previous GDM than women who had not had GDM (20% vs 7%, P = 0.02). Women who previously had GDM did not exhibit a higher incidence of preconception planning or folate supplementation. Conclusions It is common for women with Type 2 diabetes in pregnancy to have had GDM previously. The diagnosis of GDM is an opportunity to improve future pregnancy planning and outcomes for women with Type 2 diabetes in pregnancy. This goal is yet to be realized.
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Accepted Article
Introduction In developed countries, gestational diabetes (GDM) affects some 5–10% of the pregnant population [1]. GDM is associated with a trilogy of risks: perinatal morbidity, predisposition of the offspring to a diabetogenic phenotype, and it is an indicator that the mother is at high risk of developing diabetes in the future [2]. The long-term risk of maternal diabetes is around 50%, 3.5–7 times that of women who did not have GDM in pregnancy [1,3–5]. It has been estimated that up to one third of women who ultimately develop Type 2 diabetes may have had an earlier GDM pregnancy [1]. Development of Type 2 diabetes before or within a woman’s reproductive years has additional implications, because the presence of pre-existing diabetes in pregnancy is associated with more severe pregnancy outcomes such as miscarriage, fetal malformation and stillbirth [6]. Because the high risk of the mother developing diabetes following GDM is well known, guidelines generally recommend regular screening for diabetes after a GDM pregnancy, some with a greater intensity of testing while the woman is still in her reproductive years.
In some developed countries, Type 2 diabetes is now at least as common as Type 1 diabetes in pregnancy [7], and the outcomes are generally no better [7–10]. Although pre-pregnancy planning and counselling are known to improve the outcomes of diabetic pregnancy [11,12], women with Type 2 diabetes are often inadequately aware of, or are unable to fully contemplate, the potential implications of a diabetic pregnancy. Thus specialist attention may not be sought until after pregnancy has occurred. However, women with GDM are already identified by health services, and receive diabetes and lifestyle training during pregnancy. This exposure to diabetes
This article is protected by copyright. All rights reserved.
Accepted Article
HbA1c. This is disappointing, and highlights the need to effectively promote future pregnancy planning among women during their GDM pregnancy and prior to their next pregnancy, perhaps with novel methods of delivering this message [23]. Because there were a large number of women found to have overt diabetes in pregnancy, we speculate that despite recommendations to undertake regular diabetes screening following a GDM pregnancy, there was a failure to do so; hence these women were not identified to have diabetes until they were pregnant. The increased detection of overt diabetes in pregnancy among women who had previous GDM may be due to early testing on the part of the antenatal care team because of the past history. This again highlights the need for better education of both women and their healthcare providers of the need for regular testing for diabetes following a GDM pregnancy. Several surveys have found low rates of post-partum testing for diabetes after GDM, and longer term follow-up is equally poor [24–26]. Reminder systems have been shown to improve subsequent diabetes screening rates [27]. In Australia, a national annual reminder system was established in 2010 [28] but it remains to be seen whether this will be effective in increasing regular diabetes screening among an entire population of women who have had GDM. The adoption of HbA1c for the diagnosis will simplify testing and possibly improve annual
screening rates, but the poor correlation between HbA1c and the GTT in the post-partum period is
a factor that needs to be considered [29]. A limitation of our study is that there was incomplete data capture, and with the retrospective nature, some questions such as pre-pregnancy planning may be open to interpretation. Early screening for overt diabetes in pregnancy was conducted in an ad hoc manner, rather than systematically. Nonetheless, these issues would not alter our main finding that women with Type 2 diabetes in pregnancy often had GDM in a previous pregnancy.
This article is protected by copyright. All rights reserved.
Accepted Article
10
11
12
13
14
15
16
Macintosh MCM, Fleming KM, Bailey JA, Doyle P, Modder J, Acolet D et al. Perinatal mortality and congenital anomalies in babies of women with Type 1 or type 2 diabetes in England, Wales, and Northern Ireland: population based study. BMJ 2006; 333: 177. Ray JG, O’Brien TE, Chan WS. Preconception care and the risk of congenital anomalies in the offspring of women with diabetes mellitus: a meta-analysis. Q J Med 2001; 94: 435–444. Murphy HR, Roland JM, Skinner TC, Simmons D, Gurnell E, Morrish NJ et al. Effectiveness of a regional prepregnancy care program in women with Type 1 and type 2 diabetes. Diabetes Care 2010; 33: 2514–2520. McElduff A, Cheung NW, McIntyre HD, Lagstrom JA, Oats JJ, Ross GP et al. The Australasian Diabetes in Pregnancy Society consensus guidelines for the management of Type 1 and type 2 diabetes in relation to pregnancy. Med J Aust 2005; 183: 373–377. Ratner RE, Christophi CA, Metzger BE, Dabelea D, Bennett PH, Pi-Sunyer X et al. Prevention of diabetes in women with a history of gestational diabetes: effects of metformin and lifestyle interventions. J Clin Endocrinol Metab 2008; 93: 4774–4779. Ferrara A, Hedderson M, Albright CL, Ehrlich SF, Quesenberry CP, Peng T et al. A pregnancy and postpartum lifestyle intervention in women with GDM reduces diabetes risk factors: a feasibility randomized control trial. Diabetes Care 2011; 34: 1519–1525. Cheung NW, Smith BJ, Henriksen H, Tapsell LC, McLean M, Bauman A. A group-based healthy lifestyle program for women with previous gestational diabetes. Diabet Res Clin Pract 2007; 77: 333–334.
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Accepted Article
an increase in the annual number of cases of Type 2 diabetes in pregnancy over the period of the study (Fig. 2). In 76 (44%) cases, the woman had previously had a GDM pregnancy. Women with Type 2 diabetes in pregnancy who previously had GDM were older, have higher gravidy and parity, and have higher BMI than women who had not had a GDM pregnancy. They were also more likely to have overt diabetes in pregnancy (20% vs 7%, P = 0.02). There were no differences in indices of preconception planning, HbA1c parameters or birth outcomes. Table 1 provides a detailed
comparison between women who had previous GDM and those who had not. There was one neonatal death, the child of a woman with previous GDM who had overt diabetes in pregnancy. Of those women with known Type 2 diabetes diagnosed prior to pregnancy (i.e. not overt diabetes in pregnancy) who had previous GDM, diabetes had been diagnosed a median of 2 years prior (IQR 1–4 years, data available for 54/61 cases).
There was a difference between the hospitals in the percentage of women who had previous GDM: 42 hospital A%, 21% hospital B and 64% hospital C (P < 0.01). This may be related to a difference in parity between the hospitals, with a median parity at hospital A of 1 (IQR 0–1), at hospital B of 0 (IQR 0–1) and at hospital C of 1 (IQR 1–2), P = 0.049. There was no difference in the incidence of overt diabetes in pregnancy between the hospitals. Subanalysis of the parous women only (N = 108) did not alter the findings of the study, except that the difference in age and BMI fell out of significance. Further analysis of the 30 women who had more than one Type 2 diabetes pregnancy (31 pregnancies) was conducted to assess whether pregnancy planning was better with the second This article is protected by copyright. All rights reserved.
Accepted Article
pregnancy. Comparing the second pregnancy with the first pregnancy, there was no improvement in taking preconception folate (39% vs 29%, P = 0.47), undertaking pregnancy planning (43% vs 57%, P = 0.32), or having an HbA1c performed prior to pregnancy or in the first trimester (74%
vs 67%, P = 0.52).
Discussion In our population, half of the women who had Type 2 diabetes in pregnancy, had a prior pregnancy with GDM. It has been recognized that the risks associated with GDM include adverse perinatal outcomes, future maternal diabetes and fetal programming towards a diabetogenic phenotype [2]. We now add an additional implication of GDM; that is, future pregnancies in which the mother has Type 2 diabetes. Potentially, this may be more important than the other commonly recognized concerns of GDM, because Type 2 diabetes in pregnancy is associated with much greater morbidity and fetal mortality.
The diagnosis of GDM should facilitate the identification of women who are at risk of future diabetes, presenting the opportunity to provide long-term healthy lifestyle advice, undertake diabetes preventative measures, and implement regular screening to enable the early diagnosis of diabetes to minimize the development of diabetic complications. Pregnancy may be a favourable setting in which to initiate these measures because this, and the post-natal period, are a time when women might be particularly susceptible to modification of health behaviour. The potential of the child to develop diabetes may further motivate women to consider changes in lifestyle to reduce the family’s risk.
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Accepted Article
Lifestyle interventions or metformin administered to older women with impaired glucose tolerance and a history of GDM have been demonstrated to reduce the incidence of diabetes [14]. There is, however, a paucity of evidence that earlier intervention can be effective. Studies of lifestyle interventions conducted among women soon after GDM have demonstrated that modest improvements in dietary intake and physical activity, or better weight management, are possible for some women [15,16], and women who achieve weight loss following a GDM pregnancy have lower glucose than those who do not [17]. However, to date, no randomized study has shown that any post-partum programme can prevent deterioration in glucose tolerance in this group as a whole. Family obligations, return to work, further pregnancies, cultural beliefs and psychosocial issues are all barriers to improving one’s physical activity and dietary habits, so many of these women continue less than healthy lifestyles post-partum [18–21]. The findings of the current study add impetus to the need to develop effective proximal intervention programmes, to prevent the progression to Type 2 diabetes while women are still in their reproductive years.
Although preconception planning is known to improve pregnancy outcomes, the literature indicates that the uptake of this is poor. Among women with Type 2 diabetes, this generally occurs in fewer than 50% of cases [7,8,22]. In keeping with this, we found that although women with GDM may have had fair warning of the possibility of Type 2 diabetes in future pregnancies, and perhaps received advice regarding the need for future preconception planning, there were few signs that such advice was remembered or heeded. There was no improvement in the preconception use of folate supplementation, pregnancy planning, recall of formal preconception counselling, early presentation for pregnancy care or in diabetes control as determined by the
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Accepted Article
HbA1c. This is disappointing, and highlights the need to effectively promote future pregnancy planning among women during their GDM pregnancy and prior to their next pregnancy, perhaps with novel methods of delivering this message [23]. Because there were a large number of women found to have overt diabetes in pregnancy, we speculate that despite recommendations to undertake regular diabetes screening following a GDM pregnancy, there was a failure to do so; hence these women were not identified to have diabetes until they were pregnant. The increased detection of overt diabetes in pregnancy among women who had previous GDM may be due to early testing on the part of the antenatal care team because of the past history. This again highlights the need for better education of both women and their healthcare providers of the need for regular testing for diabetes following a GDM pregnancy. Several surveys have found low rates of post-partum testing for diabetes after GDM, and longer term follow-up is equally poor [24–26]. Reminder systems have been shown to improve subsequent diabetes screening rates [27]. In Australia, a national annual reminder system was established in 2010 [28] but it remains to be seen whether this will be effective in increasing regular diabetes screening among an entire population of women who have had GDM. The adoption of HbA1c for the diagnosis will simplify testing and possibly improve annual
screening rates, but the poor correlation between HbA1c and the GTT in the post-partum period is
a factor that needs to be considered [29]. A limitation of our study is that there was incomplete data capture, and with the retrospective nature, some questions such as pre-pregnancy planning may be open to interpretation. Early screening for overt diabetes in pregnancy was conducted in an ad hoc manner, rather than systematically. Nonetheless, these issues would not alter our main finding that women with Type 2 diabetes in pregnancy often had GDM in a previous pregnancy.
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Accepted Article
We also did not have data on miscarriages and our sample size was too small to detect differences in major adverse consequences of diabetic pregnancy between the two groups. Contemporary data that women with Type 2 diabetes have pregnancy outcomes that are as poor as for women with Type 1 diabetes suggest a degree of complacency or unawareness of the risk [7–10]. Amelioration of this risk through the prevention of Type 2 diabetes, or its early detection thus providing the opportunity for optimal pre-pregnancy management, is an opportunity that should not be missed.
Twenty-five years ago, the St Vincent declaration set a target for women with diabetes to have similar pregnancy outcomes to women who do not have diabetes [30]. Although achieving normal pregnancy outcomes for women with Type 1 diabetes remains elusive, the rising tide of Type 2 diabetes will result in a greater proportion of diabetic pregnancy in this latter category, presenting an increasing challenge. Our data indicate that for many women, GDM precedes a Type 2 diabetes pregnancy. Thus there is the potential to use this earlier diagnosis of GDM as a means to ameliorate the risk of subsequent Type 2 diabetes in pregnancy. Unfortunately, this opportunity is yet to be fully utilized to achieve optimal pregnancy outcomes for women with Type 2 diabetes.
Funding sources Competing interests None declared.
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Accepted Article
References 1
2
3
4
5
6
7
8
9
Cheung NW, Byth K. The population health significance of gestational diabetes. Diabetes Care 2003; 26: 2005–2009. Moses RG, Cheung NW. Point: universal screening for gestational diabetes. Diabetes Care 2009; 32: 1349–1351. Kim C, Newton K, Knopp R. Gestational diabetes and the incidence of Type 2 diabetes: a systematic review. Diabetes Care 2002; 25: 1862–1868. Bellamy L, Casas J, Hingorani A, Williams D. Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis. Lancet 2009; 373: 1773–1779. Lee AJ, Hiscock RJ, Wein P, Walker SP, Permezel M. Gestational diabetes mellitus: clinical predictors and long-term risk of developing type 2 diabetes. Diabetes Care 2007; 30: 877–883. Kitzmiller JL, Buchanan TA, Kjos S, Combs CA, Ratner RE. Pre-conception care of diabetes, congenital malformations, and spontaneous abortions. Diabetes Care 1996; 19: 514–541. McElduff A, Ross GP, Lagström JA, Champion B, Flack JR, Lau SM et al. Pregestational diabetes and pregnancy: an Australian experience. Diabetes Care 2005; 28: 1260–1261. Diabetes in Pregnancy Group, France. French multicentric survey of outcome of pregnancy in women with pregestational diabetes. Diabetes Care 2003; 26: 2990–2993. Clausen TD, Mathiesen E, Ekbom P, Hellmuth E, Mandrup-Poulsen T, Damm P. Poor pregnancy outcome in women with type 2 diabetes. Diabetes Care 2005; 28: 323–328.
This article is protected by copyright. All rights reserved.
Accepted Article
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Macintosh MCM, Fleming KM, Bailey JA, Doyle P, Modder J, Acolet D et al. Perinatal mortality and congenital anomalies in babies of women with Type 1 or type 2 diabetes in England, Wales, and Northern Ireland: population based study. BMJ 2006; 333: 177. Ray JG, O’Brien TE, Chan WS. Preconception care and the risk of congenital anomalies in the offspring of women with diabetes mellitus: a meta-analysis. Q J Med 2001; 94: 435–444. Murphy HR, Roland JM, Skinner TC, Simmons D, Gurnell E, Morrish NJ et al. Effectiveness of a regional prepregnancy care program in women with Type 1 and type 2 diabetes. Diabetes Care 2010; 33: 2514–2520. McElduff A, Cheung NW, McIntyre HD, Lagstrom JA, Oats JJ, Ross GP et al. The Australasian Diabetes in Pregnancy Society consensus guidelines for the management of Type 1 and type 2 diabetes in relation to pregnancy. Med J Aust 2005; 183: 373–377. Ratner RE, Christophi CA, Metzger BE, Dabelea D, Bennett PH, Pi-Sunyer X et al. Prevention of diabetes in women with a history of gestational diabetes: effects of metformin and lifestyle interventions. J Clin Endocrinol Metab 2008; 93: 4774–4779. Ferrara A, Hedderson M, Albright CL, Ehrlich SF, Quesenberry CP, Peng T et al. A pregnancy and postpartum lifestyle intervention in women with GDM reduces diabetes risk factors: a feasibility randomized control trial. Diabetes Care 2011; 34: 1519–1525. Cheung NW, Smith BJ, Henriksen H, Tapsell LC, McLean M, Bauman A. A group-based healthy lifestyle program for women with previous gestational diabetes. Diabet Res Clin Pract 2007; 77: 333–334.
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Ehrlich SF, Hedderson MM, Quesenberry CP, Feng J, Brown SD, Crites Y et al. Postpartum weight loss and glucose metabolism in women with gestational diabetes: the DEBI Study. Diabet Med 2014; 31: 862–867. Smith BJ, Cheung NW, Zehle K, McLean M, Bauman AE. Post-partum physical activity and related psychosocial factors among women with recent gestational diabetes. Diabetes Care 2005; 28: 2650–2654. Zehle K, Smith BJ, Chey T, McLean M, Bauman AE, Cheung NW. Psychosocial factors related to diet among women with recent gestational diabetes: opportunities for intervention. Diabet Educ 2008; 34: 807–814. Razee H, van der Ploeg HP, Blignault I, Smith BJ, Bauman AE, McLean M et al. Investigating modifiable determinants of type 2 diabetes in women with recent gestational diabetes: a cross cultural qualitative study. Health Prom J Aust 2010; 21: 130–137. Keiffer EC, Sinco B, Kim C. Health behaviours among women of reproductive age with and without a history of gestational diabetes mellitus. Diabetes Care 2006; 29: 1788– 1793. Roland JM, Murphy HR, Ball V, Northcote-Wright J, Temple RC. The pregnancies of women with type 2 diabetes: poor outcomes but opportunities for improvement. Diabet Med 2005; 22: 1774–1777. Holmes VA, Spence M, McCance D, Patterson CC, Harper R, Alderice FA. Evaluation of a DVD for women with diabetes: impact on knowledge and attitudes to preconception care. Diabet Med 2012; 29: 950–956.
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Kim C, Tabaei BP, Burke R McEwen LN, Lash RW, Johnson SL et al. Missed opportunities for type 2 diabetes mellitus screening among women with a history of gestational diabetes mellitus. Am J Public Health 2006; 96: 1643–1648. Russell MA, Phipps MG, Olson CL, Welch HG, Carpenter MW. Rates of postpartum glucose testing after gestational diabetes mellitus. Obstet Gynecol 2006; 108: 1456–1462. McGovern A, Butler L, Jones S, van Vlymen J, Sadek K, Munro N et al. Diabetes screening after gestational diabetes in England: a quantitative retrospective cohort study. Br J Gen Pract 2014; 64: e17–23. Clark HD, Graham ID, Karovitch A, Keely EJ. Do postal reminders increase postpartum screening of diabetes mellitus in women with gestational diabetes mellitus? A randomised controlled trial. Am J Obstet Gynecol 2009; 200: 634.e1–7. National Diabetes Services Scheme. http://www.ndss.com.au/en/GD/Diabetes-Register/ Last accessed 24 April 2014. Kim C, Herman WH, Cheung NW, Gunderson EP, Richardson C. Comparison of hemoglobin A1c with fasting plasma glucose and 2-hour post-challenge glucose for risk stratification among women with recent gestational diabetes mellitus. Diabetes Care 2011; 34: 1949–1951. Workshop Report. Diabetes care and research in Europe: The Saint Vincent declaration. Diabet Med 1990; 7: 360.
FIGURE 1 Classification of cases of Type 2 diabetes in pregnancy in the study. FIGURE 2 Pregnancies in which the mother had Type 2 diabetes by year. Data from all three hospitals for 1997–2007, two hospitals for 2008 and one hospital for 2009 (both shaded).
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Accepted Article
Table 1 Type 2 diabetes in pregnancy. Recurrent episodes of Type 2 diabetes in pregnancy are excluded. Cases in which the mother had previously had GDM compared with those who had not had GDM.
Age
Previous GDM (N = 76)
No previous GDM
Number of subjects or
(N = 96)
Median (IQR)
Number subjects or
P
Median (IQR) 33 (31–37)
31 (28–36)
< 0.01
Australian born
31/76 (41%)
33/94 (35%)
0.45
First-degree family
50/72 (70%)
56/84 (69%)
0.52
Gravida
3 (2–5)
2 (1–2)
Received Date : 23-Jul-2014 Revised Date : 10-Nov-2014 Accepted Date : 09-Feb-2015 Article type
: Research Article
Gestational diabetes: a red flag for future Type 2 diabetes in pregnancy? A retrospective analysis
N. W. Cheung1,2, A. Lih1,2, S. M. Lau1, K. Park2, S. Padmanabhan1 and A. McElduff3
1
Department of Diabetes & Endocrinology, Westmead Hospital, Sydney, 2Department of
Diabetes & Endocrinology, Nepean Hospital, Sydney, 3The Northern Sydney Endocrine Centre
and Royal North Shore Hospital, Sydney, Australia
Correspondence to: N. Wah Cheung. E-mail: [email protected]
What’s new? •
We found that almost half the women with Type 2 diabetes in pregnancy previously had gestational diabetes.
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/dme.12723 This article is protected by copyright. All rights reserved.
Accepted Article
•
Gestational diabetes is an opportunity to discuss and improve future pregnancy planning, particularly with respect to Type 2 diabetes in pregnancy.
Abstract Aims This study sought to understand the relationship between Type 2 diabetes in pregnancy and previous gestational diabetes (GDM), and determine whether a previous pregnancy with GDM was associated with subsequent better pregnancy planning. Methods A retrospective review of medical records of women with Type 2 diabetes in pregnancy was conducted at three teaching hospitals to ascertain whether they had earlier GDM, and to determine whether this is associated with differences in measures of pregnancy planning and diabetes management. Results Of 172 index pregnancies affected by Type 2 diabetes, in 76 (44%) cases, the mother had a previous history of GDM. Within this cohort, a diagnosis of ‘overt diabetes in pregnancy’, made on the basis of a GTT result during pregnancy in the WHO diabetic range with persistent diabetes post partum, was more common among women who had previous GDM than women who had not had GDM (20% vs 7%, P = 0.02). Women who previously had GDM did not exhibit a higher incidence of preconception planning or folate supplementation. Conclusions It is common for women with Type 2 diabetes in pregnancy to have had GDM previously. The diagnosis of GDM is an opportunity to improve future pregnancy planning and outcomes for women with Type 2 diabetes in pregnancy. This goal is yet to be realized.
This article is protected by copyright. All rights reserved.
Accepted Article
Introduction In developed countries, gestational diabetes (GDM) affects some 5–10% of the pregnant population [1]. GDM is associated with a trilogy of risks: perinatal morbidity, predisposition of the offspring to a diabetogenic phenotype, and it is an indicator that the mother is at high risk of developing diabetes in the future [2]. The long-term risk of maternal diabetes is around 50%, 3.5–7 times that of women who did not have GDM in pregnancy [1,3–5]. It has been estimated that up to one third of women who ultimately develop Type 2 diabetes may have had an earlier GDM pregnancy [1]. Development of Type 2 diabetes before or within a woman’s reproductive years has additional implications, because the presence of pre-existing diabetes in pregnancy is associated with more severe pregnancy outcomes such as miscarriage, fetal malformation and stillbirth [6]. Because the high risk of the mother developing diabetes following GDM is well known, guidelines generally recommend regular screening for diabetes after a GDM pregnancy, some with a greater intensity of testing while the woman is still in her reproductive years.
In some developed countries, Type 2 diabetes is now at least as common as Type 1 diabetes in pregnancy [7], and the outcomes are generally no better [7–10]. Although pre-pregnancy planning and counselling are known to improve the outcomes of diabetic pregnancy [11,12], women with Type 2 diabetes are often inadequately aware of, or are unable to fully contemplate, the potential implications of a diabetic pregnancy. Thus specialist attention may not be sought until after pregnancy has occurred. However, women with GDM are already identified by health services, and receive diabetes and lifestyle training during pregnancy. This exposure to diabetes
This article is protected by copyright. All rights reserved.
Accepted Article
HbA1c. This is disappointing, and highlights the need to effectively promote future pregnancy planning among women during their GDM pregnancy and prior to their next pregnancy, perhaps with novel methods of delivering this message [23]. Because there were a large number of women found to have overt diabetes in pregnancy, we speculate that despite recommendations to undertake regular diabetes screening following a GDM pregnancy, there was a failure to do so; hence these women were not identified to have diabetes until they were pregnant. The increased detection of overt diabetes in pregnancy among women who had previous GDM may be due to early testing on the part of the antenatal care team because of the past history. This again highlights the need for better education of both women and their healthcare providers of the need for regular testing for diabetes following a GDM pregnancy. Several surveys have found low rates of post-partum testing for diabetes after GDM, and longer term follow-up is equally poor [24–26]. Reminder systems have been shown to improve subsequent diabetes screening rates [27]. In Australia, a national annual reminder system was established in 2010 [28] but it remains to be seen whether this will be effective in increasing regular diabetes screening among an entire population of women who have had GDM. The adoption of HbA1c for the diagnosis will simplify testing and possibly improve annual
screening rates, but the poor correlation between HbA1c and the GTT in the post-partum period is
a factor that needs to be considered [29]. A limitation of our study is that there was incomplete data capture, and with the retrospective nature, some questions such as pre-pregnancy planning may be open to interpretation. Early screening for overt diabetes in pregnancy was conducted in an ad hoc manner, rather than systematically. Nonetheless, these issues would not alter our main finding that women with Type 2 diabetes in pregnancy often had GDM in a previous pregnancy.
This article is protected by copyright. All rights reserved.
Accepted Article
10
11
12
13
14
15
16
Macintosh MCM, Fleming KM, Bailey JA, Doyle P, Modder J, Acolet D et al. Perinatal mortality and congenital anomalies in babies of women with Type 1 or type 2 diabetes in England, Wales, and Northern Ireland: population based study. BMJ 2006; 333: 177. Ray JG, O’Brien TE, Chan WS. Preconception care and the risk of congenital anomalies in the offspring of women with diabetes mellitus: a meta-analysis. Q J Med 2001; 94: 435–444. Murphy HR, Roland JM, Skinner TC, Simmons D, Gurnell E, Morrish NJ et al. Effectiveness of a regional prepregnancy care program in women with Type 1 and type 2 diabetes. Diabetes Care 2010; 33: 2514–2520. McElduff A, Cheung NW, McIntyre HD, Lagstrom JA, Oats JJ, Ross GP et al. The Australasian Diabetes in Pregnancy Society consensus guidelines for the management of Type 1 and type 2 diabetes in relation to pregnancy. Med J Aust 2005; 183: 373–377. Ratner RE, Christophi CA, Metzger BE, Dabelea D, Bennett PH, Pi-Sunyer X et al. Prevention of diabetes in women with a history of gestational diabetes: effects of metformin and lifestyle interventions. J Clin Endocrinol Metab 2008; 93: 4774–4779. Ferrara A, Hedderson M, Albright CL, Ehrlich SF, Quesenberry CP, Peng T et al. A pregnancy and postpartum lifestyle intervention in women with GDM reduces diabetes risk factors: a feasibility randomized control trial. Diabetes Care 2011; 34: 1519–1525. Cheung NW, Smith BJ, Henriksen H, Tapsell LC, McLean M, Bauman A. A group-based healthy lifestyle program for women with previous gestational diabetes. Diabet Res Clin Pract 2007; 77: 333–334.
This article is protected by copyright. All rights reserved.
Accepted Article
an increase in the annual number of cases of Type 2 diabetes in pregnancy over the period of the study (Fig. 2). In 76 (44%) cases, the woman had previously had a GDM pregnancy. Women with Type 2 diabetes in pregnancy who previously had GDM were older, have higher gravidy and parity, and have higher BMI than women who had not had a GDM pregnancy. They were also more likely to have overt diabetes in pregnancy (20% vs 7%, P = 0.02). There were no differences in indices of preconception planning, HbA1c parameters or birth outcomes. Table 1 provides a detailed
comparison between women who had previous GDM and those who had not. There was one neonatal death, the child of a woman with previous GDM who had overt diabetes in pregnancy. Of those women with known Type 2 diabetes diagnosed prior to pregnancy (i.e. not overt diabetes in pregnancy) who had previous GDM, diabetes had been diagnosed a median of 2 years prior (IQR 1–4 years, data available for 54/61 cases).
There was a difference between the hospitals in the percentage of women who had previous GDM: 42 hospital A%, 21% hospital B and 64% hospital C (P < 0.01). This may be related to a difference in parity between the hospitals, with a median parity at hospital A of 1 (IQR 0–1), at hospital B of 0 (IQR 0–1) and at hospital C of 1 (IQR 1–2), P = 0.049. There was no difference in the incidence of overt diabetes in pregnancy between the hospitals. Subanalysis of the parous women only (N = 108) did not alter the findings of the study, except that the difference in age and BMI fell out of significance. Further analysis of the 30 women who had more than one Type 2 diabetes pregnancy (31 pregnancies) was conducted to assess whether pregnancy planning was better with the second This article is protected by copyright. All rights reserved.
Accepted Article
pregnancy. Comparing the second pregnancy with the first pregnancy, there was no improvement in taking preconception folate (39% vs 29%, P = 0.47), undertaking pregnancy planning (43% vs 57%, P = 0.32), or having an HbA1c performed prior to pregnancy or in the first trimester (74%
vs 67%, P = 0.52).
Discussion In our population, half of the women who had Type 2 diabetes in pregnancy, had a prior pregnancy with GDM. It has been recognized that the risks associated with GDM include adverse perinatal outcomes, future maternal diabetes and fetal programming towards a diabetogenic phenotype [2]. We now add an additional implication of GDM; that is, future pregnancies in which the mother has Type 2 diabetes. Potentially, this may be more important than the other commonly recognized concerns of GDM, because Type 2 diabetes in pregnancy is associated with much greater morbidity and fetal mortality.
The diagnosis of GDM should facilitate the identification of women who are at risk of future diabetes, presenting the opportunity to provide long-term healthy lifestyle advice, undertake diabetes preventative measures, and implement regular screening to enable the early diagnosis of diabetes to minimize the development of diabetic complications. Pregnancy may be a favourable setting in which to initiate these measures because this, and the post-natal period, are a time when women might be particularly susceptible to modification of health behaviour. The potential of the child to develop diabetes may further motivate women to consider changes in lifestyle to reduce the family’s risk.
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Lifestyle interventions or metformin administered to older women with impaired glucose tolerance and a history of GDM have been demonstrated to reduce the incidence of diabetes [14]. There is, however, a paucity of evidence that earlier intervention can be effective. Studies of lifestyle interventions conducted among women soon after GDM have demonstrated that modest improvements in dietary intake and physical activity, or better weight management, are possible for some women [15,16], and women who achieve weight loss following a GDM pregnancy have lower glucose than those who do not [17]. However, to date, no randomized study has shown that any post-partum programme can prevent deterioration in glucose tolerance in this group as a whole. Family obligations, return to work, further pregnancies, cultural beliefs and psychosocial issues are all barriers to improving one’s physical activity and dietary habits, so many of these women continue less than healthy lifestyles post-partum [18–21]. The findings of the current study add impetus to the need to develop effective proximal intervention programmes, to prevent the progression to Type 2 diabetes while women are still in their reproductive years.
Although preconception planning is known to improve pregnancy outcomes, the literature indicates that the uptake of this is poor. Among women with Type 2 diabetes, this generally occurs in fewer than 50% of cases [7,8,22]. In keeping with this, we found that although women with GDM may have had fair warning of the possibility of Type 2 diabetes in future pregnancies, and perhaps received advice regarding the need for future preconception planning, there were few signs that such advice was remembered or heeded. There was no improvement in the preconception use of folate supplementation, pregnancy planning, recall of formal preconception counselling, early presentation for pregnancy care or in diabetes control as determined by the
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HbA1c. This is disappointing, and highlights the need to effectively promote future pregnancy planning among women during their GDM pregnancy and prior to their next pregnancy, perhaps with novel methods of delivering this message [23]. Because there were a large number of women found to have overt diabetes in pregnancy, we speculate that despite recommendations to undertake regular diabetes screening following a GDM pregnancy, there was a failure to do so; hence these women were not identified to have diabetes until they were pregnant. The increased detection of overt diabetes in pregnancy among women who had previous GDM may be due to early testing on the part of the antenatal care team because of the past history. This again highlights the need for better education of both women and their healthcare providers of the need for regular testing for diabetes following a GDM pregnancy. Several surveys have found low rates of post-partum testing for diabetes after GDM, and longer term follow-up is equally poor [24–26]. Reminder systems have been shown to improve subsequent diabetes screening rates [27]. In Australia, a national annual reminder system was established in 2010 [28] but it remains to be seen whether this will be effective in increasing regular diabetes screening among an entire population of women who have had GDM. The adoption of HbA1c for the diagnosis will simplify testing and possibly improve annual
screening rates, but the poor correlation between HbA1c and the GTT in the post-partum period is
a factor that needs to be considered [29]. A limitation of our study is that there was incomplete data capture, and with the retrospective nature, some questions such as pre-pregnancy planning may be open to interpretation. Early screening for overt diabetes in pregnancy was conducted in an ad hoc manner, rather than systematically. Nonetheless, these issues would not alter our main finding that women with Type 2 diabetes in pregnancy often had GDM in a previous pregnancy.
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We also did not have data on miscarriages and our sample size was too small to detect differences in major adverse consequences of diabetic pregnancy between the two groups. Contemporary data that women with Type 2 diabetes have pregnancy outcomes that are as poor as for women with Type 1 diabetes suggest a degree of complacency or unawareness of the risk [7–10]. Amelioration of this risk through the prevention of Type 2 diabetes, or its early detection thus providing the opportunity for optimal pre-pregnancy management, is an opportunity that should not be missed.
Twenty-five years ago, the St Vincent declaration set a target for women with diabetes to have similar pregnancy outcomes to women who do not have diabetes [30]. Although achieving normal pregnancy outcomes for women with Type 1 diabetes remains elusive, the rising tide of Type 2 diabetes will result in a greater proportion of diabetic pregnancy in this latter category, presenting an increasing challenge. Our data indicate that for many women, GDM precedes a Type 2 diabetes pregnancy. Thus there is the potential to use this earlier diagnosis of GDM as a means to ameliorate the risk of subsequent Type 2 diabetes in pregnancy. Unfortunately, this opportunity is yet to be fully utilized to achieve optimal pregnancy outcomes for women with Type 2 diabetes.
Funding sources Competing interests None declared.
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FIGURE 1 Classification of cases of Type 2 diabetes in pregnancy in the study. FIGURE 2 Pregnancies in which the mother had Type 2 diabetes by year. Data from all three hospitals for 1997–2007, two hospitals for 2008 and one hospital for 2009 (both shaded).
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Table 1 Type 2 diabetes in pregnancy. Recurrent episodes of Type 2 diabetes in pregnancy are excluded. Cases in which the mother had previously had GDM compared with those who had not had GDM.
Age
Previous GDM (N = 76)
No previous GDM
Number of subjects or
(N = 96)
Median (IQR)
Number subjects or
P
Median (IQR) 33 (31–37)
31 (28–36)
< 0.01
Australian born
31/76 (41%)
33/94 (35%)
0.45
First-degree family
50/72 (70%)
56/84 (69%)
0.52
Gravida
3 (2–5)
2 (1–2)
